Advances in techniques for red blood cell storage have made feasible the prolonged liquid storage of red blood cell concentrates for 42 days, which allows red blood cells to be readily available for transfusion to anemic patients. For example, even surgical procedures associated with very large, acute blood losses can now be performed given the ready availability of red blood cells for transfusion. To maintain adequate tissue oxygenation during acute blood loss. 1) lost blood volume must be adequately replaced by crystalloid or colloid solutions to maintain tissue perfusion, and 2) lost red blood cells must be adequately replaced by red blood cell transfusion to maintain adequate oxygen-carrying capacity. This proposal is directed toward the later of these two requirements. Red blood cells are transfused to prevent or treat inadequate tissue oxygenation. Currently, tissue oxygenation is not directly measured, and as a result, transfusion of red blood cells are based on vague clinical criteria, especially when the hemoglobin, concentrations is between 7 and 10 g/dL. It is the objective of this proposal to directly measure tissue oxygen in humans during acute normovolemic anemia and red blood cell transfusion. To accomplish this objective, we will study tissue oxygen in accessible tissues (whole-body and local oxygenation) in 196 human subjects. Three groups of subjects will be studied; 1) healthy subjects who undergo acute normovolemic hemodilution, in whom whole-body and subcutaneous oxygenation will be simultaneously measured, 2) posterior spine fusion patients, who develop acute normovolemic anemia due to surgical blood loss, in whom subcutaneous oxygenation will be measured, and 3) major hepatectomy patients who develop acute normovolemic anemia due to surgical blood loss, in whom subcutaneous, gastrointestinal serosal surface and gastric mucosal oxygenation will be measured. In addition, subcutaneous tissue oxygen will be measured immediately and 24 hours after red blood cell transfusion. Data from this proposal will provide information as to whether and how tissue oxygen decreases in acute normovolemic anemia in humans, and whether and when tissue oxygen increases with red blood cell transfusion. This research is directly responsive to the RFA-s area of emphasis: "Indications for red blood cell transfusion.